The long-term objective of this project is a better understanding of the role of genetic and environmental factors in human neuropsychiatric disorders through the study of autism. Understanding the genetic and epigenetic factors important for the manifestation of autism and associated behaviors will be of direct benefit to patients concerned about recurrence in their families; ultimately, clarifying the genetics of these conditions may elucidate their pathogenesis. We will collect data that will make it possible to characterize more completely the nature of the relationship between autism, social and cognitive difficulties, neuropsychological profiles and other neuropsychiatric conditions. We propose to collect a sample of 92 families of high functioning (non-retarded) autistic probands, 1 18 families of Asperger syndrome probands and 50 families of age and gender matched controls. These samples will be combined with the samples already collected in this ongoing study, so that final samples will be comprised of 160 families of HFA probands, 160 families of AS probands and 140 multiplex families in which at least two children have autism. These data will allow a direct comparison of families to determine the extent that a 'broader phenotype' represents a milder manifestation of autism and whether Asperger's syndrome is etiologically related to this spectrum of behaviors. Studying these families should help to clarify further the transmission of autism and related conditions and to further our understanding of the familial relationship between autism and Asperger's syndrome. The data about psychopathology will allow analyses to examine the relationship of this spectrum to specific psychiatric conditions. We plan to include all multiplex families ascertained for the Molecular Genetics project in these analyses to examine whether the phenotype in these families is similar to that observed in families where there is only one child with autism and/or Asperger's syndrome. In all cases, information will be obtained by direct structured assessment of all pertinent family members. These assessments will include an extensive neuropsychological assessment, structured interviews for the assessment of autism and related conditions and structured psychiatric interviews for the documentation of all major psychiatric disorders.